Research in the Hogle lab employs a variety of biophysical, biochemical and molecular approaches to probe the relationship between virus structure and function. The work in the lab is currently focused in three main areas 1) the cell entry pathway of poliovirus and related picornaviruses, 2) herpes virus replication proteins, 3) antiviral design. 1) Although poliovirus and related small icosahedral viruses are relatively simple and arguably the best understood viral pathogens, they must perform a variety of biological functions at various stages of their life cycle, many of which, including cell-entry, remain poorly understood. Understanding the cell entry pathway of simple viruses poses structural questions that span more than six orders of magnitude in scale ranging from the atomic level (tenths of nanometers) to the cellular level (tens of microns). Our studies of poliovirus cell entry therefore employ a multidisciplinary approach, including the use of single molecule techniques to follow the pathways leading to release of the viral genome during normal infection (in collaboration with Xiaowei Zhuang), the development of receptor- decorated liposomes and tethered bilayers as simple model systems for biochemical and structural characterization of the early events during infection, structural studies of soluble and membrane-bound virus-receptor complexes and cell entry intermediates using electron cryo-electron microscopy, and cryo-electron tomography, and structural studies of cell entry intermediates in cells using correlative microscopy (an approach which combines fluorescence microscopy and electron tomography) of both fixed and frozen samples. 2) In collaboration with Don Coen, we have initiated a program of structural studies of essential proteins from herpes viruses. We have solved the structures of the processivity factor from herpes simplex virus (UL42) in complex with a peptide from the C-terminus of the catalytic subunit of the polymerase, the processivity factor from cytomegalovirus (UL44) alone and in complex with a peptide from the C-terminus of its polymerase, and the processivity factor from human herpes virus 8 (PF8). We are also pursuing structural studies processivity factor/DNA complexes and of the nuclear egress complex of human and murine cytomegalovirus. 3) Our interest in structures of viruses and viral proteins has naturally led us to investigate methods for using the structures to design antiviral drugs.